The long-term objective of this research is to develop a detailed, atomic-resolution structural and functional understanding of protein aggregation and fibrillation relevant to human disease, principally with studies of alpha-synuclein. Wild type alpha-synuclein and its mutants (A30P, E46K and A53T) associated with early- onset Parkinson's disease (PD) will be examined in several structural states, including protofibrils, fibrils and membrane-associated complexes. We propose that the chemical details of these structures determine the natural physiological function of alpha-synuclein and, in the mutants and/or under environmental stress, contribute to PD pathology. Moreover, we propose that conversion among several structural states is an essential feature of synucleins; this structural plasticity is likely to be required for neuronal development and maintenance. To examine these structures, magic-angle spinning (MAS) solid-state NMR (SSNMR) experiments will be employed, elucidating details of conformation and dynamics that are inaccessible to other experimental techniques.